Tau isoform regulation in neurodegenerative diseases

Ian D'Souza, PhD
University of Washington School of Medicine (Seattle, WA)
Year Awarded:
Grant Duration:
April 1, 2004 to March 31, 2006
Alzheimer's Disease
Award Amount:
Grant Reference ID:
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US Northwestern

Tau isoform regulation in neurodegenerative diseases


Dementia affects more than 20 million people worldwide and more than 4 million people in the United States. Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two of the most common forms of dementia. Toxic, insoluble aggregates of tau protein, called neurofibrillary tangles (NFTs) are pathological signatures in AD and FTD. The amount of tau accumulation correlates with disease severity, but its role in the initiation of the disease is unknown. The objective of Dr. D'Souza's research is to understand the mechanism for tau gene expression during normal development, normal aging, and disease development in cell cultures and mouse neuronal systems. Mice bred to express the human tau genomic construct will be a powerful system to study tau gene expression during brain development and aging, and could help identify new candidates for therapeutic interventions.


D'Souza, I. and Schellenberg, G.D. (2006) Arginine/serine-rich protein interaction domain-dependent modulation of a tau exon 10 splicing enhancer: altered interactions and mechanisms for functionally antagonistic FTDP-17 mutations Delta280K and N279K. Journal of Biological Chemistry. 281(5):2460-2469.  

Malkani, R., D'Souza, I., Gwinn-Hardy, K., Schellenberg, G.D., Hardy, J., and Momeni, P. (2006) A MAPT mutation in a regulatory element upstream of exon 10 causes frontotemporal dementia. Neurobiology of Disease. 22(2):401-403.  

D'Souza, I. and Schellenberg, G.D. (2005) Regulation of tau isoform expression and dementia. Biochim Biophys Acta. Jan 3;1739(2-3):104-15.  

Gallo, J.M., Jin, P., Thornton, C.A., Lin, H., Robertson, J., D'Souza, I., and Schlaepfer, W.W. (2005) The role of RNA and RNA processing in neurodegeneration. Journal of Neuroscience. 25(45):10372-10375.  

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